犬尿喹啉酸减轻实验性变应性鼻炎：AhR相关黏膜免疫稳态调节的证据。

文献信息

中文摘要

背景： 变应性鼻炎（AR）是一种慢性炎症性气道疾病，其特征为2型免疫反应失调和黏膜免疫调节受损。犬尿喹啉酸（KYNA）是一种具有免疫调节特性的内源性色氨酸代谢产物，可能影响炎症通路，但其在AR中的机制仍不清楚。本研究在卵清蛋白（OVA）诱导的AR大鼠模型中研究KYNA，并探讨芳香烃受体（AhR）信号的作用。
方法： 将大鼠分为对照组、AR组、溶媒组、KYNA组、地氯雷他定组和KYNA+AhR拮抗剂（CH223191）组。在OVA致敏和激发后，评估行为反应、血清炎症标志物、鼻部AhR相关蛋白、调节性细胞因子以及鼻和脾组织的组织病理学变化。
结果： OVA诱导了典型的过敏反应，包括打喷嚏和鼻部抓挠增加、血清IgE、IL-4和IL-6升高，以及鼻和脾组织明显的炎症变化。KYNA显著减轻行为症状、全身炎症介质、上皮损伤和炎症浸润，其全身效应与地氯雷他定相当，但在改善鼻部抓挠和脾组织病理学方面更优。KYNA恢复了鼻部AhR和CYP1A1表达，并增加IL-10和TGF-β，而CH223191部分减弱了这些效应，表明AhR信号参与其中。地氯雷他定对局部调节性细胞因子影响有限。组织病理学分析证实KYNA治疗后鼻和脾结构改善。
结论： 总之，KYNA通过全身抗炎作用和恢复黏膜免疫调节减轻实验性AR。AhR信号参与这些效应，特别是在CYP1A1和细胞因子调节方面，同时可能还涉及其他机制。这些发现支持KYNA作为变应性气道疾病中潜在的免疫代谢调节剂。

英文摘要

BACKGROUND: Allergic rhinitis (AR) is a chronic inflammatory airway disease characterized by dysregulated type 2 immune responses and impaired mucosal immune regulation. Kynurenic acid (KYNA), an endogenous tryptophan metabolite with immunomodulatory properties, may influence inflammatory pathways, but its mechanisms in AR remain unclear. This study investigated KYNA in an ovalbumin (OVA)-induced rat model of AR and examined the role of aryl hydrocarbon receptor (AhR) signaling.
METHODS: Rats were assigned to control, AR, vehicle, KYNA, desloratadine, and KYNA + AhR antagonist (CH223191) groups. Following OVA sensitization and challenge, behavioral responses, serum inflammatory markers, nasal AhR-associated proteins, regulatory cytokines, and histopathological changes in nasal and splenic tissues were evaluated.
RESULTS: OVA induced typical allergic responses, including increased sneezing and nasal scratching, elevated serum IgE, IL-4, and IL-6, and marked inflammatory changes in nasal and splenic tissues. KYNA significantly reduced behavioral symptoms, systemic inflammatory mediators, epithelial damage, and inflammatory infiltration, with systemic effects comparable to desloratadine but greater improvement in nasal scratching and splenic histopathology. KYNA restored nasal AhR and CYP1A1 expression and increased IL-10 and TGF-β, whereas CH223191 partially attenuated these effects, indicating involvement of AhR signaling. Desloratadine showed limited effects on local regulatory cytokines. Histopathological analysis confirmed improved nasal and splenic architecture following KYNA treatment.
CONCLUSION: In conclusion, KYNA attenuates experimental AR through systemic anti-inflammatory effects and restoration of mucosal immune regulation. AhR signaling contributes to these effects, particularly in CYP1A1 and cytokine regulation, while additional mechanisms may also be involved. These findings support KYNA as a potential immunometabolic modulator in allergic airway disease.